Gram-positive Bloodstream Infections Research Articles

An Update on Recent Clinical Trial Data in Bloodstream Infection

Bloodstream infections (BSIs) remain a significant source of morbidity and mortality globally, exacerbated by an ageing population and rising antimicrobial resistance (AMR). This review offers an updated evaluation of randomized clinical trials (RCTs) in BSI management from 2018 onwards, focusing on the evolving landscape of diagnostics and treatment. New rapid diagnostic technologies and shorter antimicrobial courses have transformed clinical practice, reducing the time to appropriate therapy and hospital stays. Several RCTs demonstrated that rapid phenotypic and genotypic tests shorten the time to optimal therapy, especially when paired with antimicrobial stewardship. Ongoing trials are investigating novel antimicrobial regimens and the safety of early oral switch strategies, particularly for Gram-positive and Gram-negative BSIs. Recent RCTs on Staphylococcus aureus BSI (SAB) and multidrug-resistant Gram-negative bacteria highlight advances in treatment but emphasize the need for further study into the efficacy of combination therapies and the utility of rapid diagnostics in different healthcare settings. The review also explores challenges in trail design, with adaptive and pragmatic appropriates improving the efficacy of clinical trials. Finally, this paper identifies gaps in the research, including the need for further investigation into oral step-down therapy, optimal durations, and the role of rapid diagnostics in resource-limited settings.

Distinguishing Gram-Positive and Gram-Negative Bloodstream Infections through Leukocytes, C-reactive protein, Procalcitonin, and D-Dimer: An Empirical Antibiotic Guidance.

This retrospective study aimed to compare the difference of the levels of white blood cells (WBC), C-reactive protein (CRP), procalcitonin, and D-Dimer in the bloodstream infection (BSI) patients, and their values in distinguishing bacterial categories. A total of 847 bloodstream infection patients were analyzed and divided into Gram-positive BSI (GP-BSI) and Gram-negative BSI (GN-BSI) groups. Most frequently isolated pathogens in GP-BSI were Staphylococcus epidermidis (35.75%), followed by Staphylococcus hominis (18.33%), and Streptococcus haemolyticus (10.16%), while in GN-BSI, Escherichia coli (30.07%), Klebsiella pneumoniae (23.98%), and Acinetobacter baumannii (13.18%) were the most common. The predictive value was evaluated based on three years of patient data, which showed an area under the curve (AUC) of 0.828. It was further validated using two years of data, which yielded an AUC of 0.925. Significant differences existed in the procalcitonin, D-Dimer, and CRP levels between GN-BSI and GP-BSI. The current results provide a more effective strategy for early differential diagnosis in bacterial categorization of BSI when combining WBC, CRP, procalcitonin, and D-Dimer measurements.

Continued Intravenous Versus First Week Transition to Oral Antibiotic Therapy in Bloodstream Infections: A Systematic Review and Meta-Analysis.

Bloodstream infections (BSIs) are a major public health concern worldwide, requiring prompt and effective antibiotic therapy. Traditionally, intravenous (IV) antibiotics have been preferred for their rapid action and consistent absorption. However, interest is growing in transitioning to oral (PO) antibiotics when suitable, due to similar pharmacokinetics, improved patient outcomes, and reduced healthcare costs. This meta-analysis aims to evaluate the clinical effectiveness of switching from IV to PO antibiotics for both gram-negative and gram-positive BSIs. Scopus, Embase, and PubMed databases were comprehensively searched until March 2023. The review included randomized controlled trials and cohort studies comparing continued IV therapy with early transition from IV to PO antibiotics within the first week of admission. Inclusion criteria encompassed studies involving adult patients (≥18 years) and reporting specific outcomes such as treatment success, mortality, and hospital readmissions. Meta-analysis of 17 studies comprising 11,245 patients demonstrated higher treatment success rates overall (OR: 1.40, P=0.04), particularly in gram-negative infections (OR: 1.42, P=0.05). However, this effect was not statistically significant in the gram-positive subgroup (OR: 1.41, P=0.036). Oral switch significantly reduced all-cause mortality overall (OR: 0.35, P=0.003), especially in gram-negative infections (OR: 0.22, P=0.008), but not significantly in gram-positive infections (OR: 0.60, P=0.09). Both gram-negative and gram-positive infections benefited from shorter hospital stays (P<0.0001), despite significant heterogeneity. Hospital readmission rates did not significantly differ between IV and oral switch groups (P=0.53). Our meta-analysis suggests potential benefits of early transition from IV to PO antibiotics for BSIs, including improved treatment outcomes and shorter hospital stays without an increased risk of readmission. However, these findings are subject to selection bias, and further standardized randomized trials are essential to validate these results.

Epidemiology and Duration of Therapy in Patients with Gram-negative Bloodstream Infections: Retrospective Analysis

Background: Longer courses of antibiotics can be associated with antimicrobial resistance and adverse effects. Randomized clinical trials support treating gram-negative bloodstream infections (GN-BSI) for a shorter duration with a consensus that a seven-day course of antibiotics is appropriate for uncomplicated GN-BSI. Prior to the implementation of a GN-BSI treatment guideline at our institution, we aimed to evaluate the characteristics of patients with GN-BSI and the duration of antibiotic therapy (DOT). Method: We retrospectively reviewed adult inpatients who had a blood culture with at least 1 gram-negative organism within 6 months (November 2022 to April 2023). Patients were excluded if they had a concomitant gram-positive bloodstream infection or if they were transitioned to comfort-focused care within 48 hours of their first positive blood culture. Complicated GN-BSI was defined as exhibiting any of the following: involvement of bone, joint, endovascular system, or foreign body, an inability to achieve source control, immunocompromised status, or failure to demonstrate clinical improvement or culture clearance within 72 hours. The primary outcome of this study was the mean DOT in patients with GN-BSI. Result: 100 patients met the inclusion criteria. Escherichia coli, identified in 54 cases, emerged as the most frequent organism. Urine (41) was the predominant source of bacteremia. Cefepime (48) was the most common empiric agent used. Of the 91 patients with available ceftriaxone susceptibility results, 84% had a susceptible organism. Amongst the 51 patients classified as having a complicated GN-BSI, the leading reason was immunosuppression. Table 1 presents a comparative analysis of complicated vs. uncomplicated GN-BSI. The average DOT for complicated GN-BSI was longer than the uncomplicated infections (20 vs. 11 days, P &lt; 0 .005). Additionally, fewer patients transitioned to oral therapy in the complicated group (33% vs. 67%, P &lt; 0 .005). Conclusion: At our institution, patients with uncomplicated GN-BSI have a shorter DOT and are more likely to transition to oral therapy than those with complicated GN-BSI. However, the mean DOT for uncomplicated infections remained longer than seven days and a large number of uncomplicated GN-BSI patients did not transition to oral therapy, indicating room for improvement in local practice through antimicrobial stewardship initiatives.

Gram-Positive Blood Stream Infections in Children After Cardiac Surgery

Gram-Positive Blood Stream Infections in Children After Cardiac Surgery

Dalbavancin Sequential Therapy for Gram-Positive Bloodstream Infection: A Multicenter Observational Study.

Long-acting lipoglycopeptides such as dalbavancin may have utility in patients with Gram-positive bloodstream infections (BSI), particularly in those with barriers to discharge or who require prolonged parenteral antibiotic courses. A retrospective cohort study was performed to provide further multicenter real-world evidence on dalbavancin use as a sequential therapy for Gram-positive BSI. One hundred fifteen patients received dalbavancin with Gram-positive BSI, defined as any positive blood culture or diagnosed with infective endocarditis, from 13 centers geographically spread across the United States between July 2015 and July 2021. Patients had a mean (SD) age of 48.5 (17.5) years, the majority were male (54%), with many who injected drugs (40%). The most common infection sources (non-exclusive) were primary BSI (89%), skin and soft tissue infection (SSTI) (25%), infective endocarditis (19%), and bone and joint infection (17%). Staphylococcus aureus accounted for 72% of index cultures, coagulase-negative Staphylococcus accounted for 18%, and Streptococcus species in 16%. Dalbavancin started a median (Q1-Q3) of 10 (6-19) days after index culture collection. The most common regimen administered was dalbavancin 1500mg as one dose for 50% of cases. The primary outcome of composite clinical failure occurred at 12.2%, with 90-day mortality at 7.0% and 90-day BSI recurrence at 3.5%. Dalbavancin may serve as a useful tool in facilitating hospital discharge in patients with Gram-positive BSI. Randomized controlled trials are anticipated to validate dalbavancin as a surrogate to current treatment standards.

Oritavancin as sequential therapy for Gram-positive bloodstream infections

BackgroundOritavancin, a long-acting lipoglycopeptide approved for use in acute bacterial skin and skin structure infections, has limited data evaluating use in serious infections due to Gram-positive organisms. We aimed to assess the effectiveness and safety of oritavancin for consolidative treatment of Gram-positive bloodstream infections (BSI), including infective endocarditis (IE).MethodsWe conducted a retrospective cohort study evaluating adult patients admitted to University of Colorado Hospital from March 2016 to January 2022 who received ≥ 1 oritavancin dose for treatment of Gram-positive BSI. Patients were excluded if the index culture was drawn at an outside facility or were > 89 years of age. The primary outcome was a 90-day composite failure (clinical or microbiological failure) in those with 90-day follow-up. Secondary outcomes included individual components of the primary outcome, acute kidney injury (AKI), infusion-related reactions (IRR), and institutional cost avoidance.ResultsOverall, 72 patients were included. Mean ± SD age was 54 ± 16 years, 61% were male, and 10% had IE. Organisms most commonly causing BSI were Staphylococcus aureus (68%, 17% methicillin-resistant), followed by Streptococcus spp. (26%), and Enterococcus spp. (10%). Patients received standard-of-care antibiotics before oritavancin for a median (IQR) of 11 (5–17) days. Composite failure in the clinically evaluable population (n = 64) at 90-days occurred in 14% and was composed of clinical and microbiological failure, which occurred in 14% and 5% of patients, respectively. Three patients (4%) experienced AKI after oritavancin, and two (3%) experienced an IRR. Oritavancin utilization resulted in earlier discharge for 94% of patients corresponding to an institutional cost-avoidance of $3,055,804 (mean $44,938/patient) from 1,102 hospital days saved (mean 16 days/patient).ConclusionsThe use of oritavancin may be an effective sequential therapy for Gram-positive BSI to facilitate early discharge resulting in institutional cost avoidance.

Incidence and Outcomes of Bloodstream Infection After Arterial Aneurysm Repair: Findings From a Population-Based Study.

Limited research has focused on bloodstream infection (BSI) in patients with arterial grafts. This study aims to describe the incidence and outcomes of BSI after arterial aneurysm repair in a population-based cohort. The expanded Rochester Epidemiology Project (e-REP) was used to analyze aneurysm repairs in adults (aged ≥18 years) residing in 8 counties in southern Minnesota from January 2010 to December 2020. Electronic records were reviewed for the first episode of BSI following aneurysm repair. BSI patients were assessed for vascular graft infection (VGI) and followed for all-cause mortality. During the study, 643 patients had 706 aneurysm repairs: 416 endovascular repairs (EVARs) and 290 open surgical repairs (OSRs). Forty-two patients developed BSI during follow-up. The 5-year cumulative incidence of BSI was 4.7% (95% confidence interval [CI], 3.0%-6.4%), with rates of 4.0% (95% CI, 1.8%-6.2%) in the EVAR group and 5.8% (95% CI, 2.9%-8.6%) in the OSR group (P = .052). Thirty-nine (92.9%) BSI cases were monomicrobial, 33 of which were evaluated for VGI. VGI was diagnosed in 30.3% (10/33), accounting for 50.0% (8/16) of gram-positive BSI cases compared to 11.8% (2/17) of gram-negative BSI cases (P = .017). The 1-, 3-, and 5-year cumulative post-BSI all-cause mortality rates were 22.2% (95% CI, 8.3%-34.0%), 55.8% (95% CI, 32.1%-71.2%), and 76.8% (95% CI, 44.3%-90.3%), respectively. The incidence of BSI following aneurysm repair was overall low. VGI was more common with gram-positive compared to gram-negative BSI. All-cause mortality following BSI was high, which may be attributed to advanced age and significant comorbidities in our cohort.

The emergence of multidrug-resistant Gram-positive bloodstream infections in India - a single center prospective cohort study.

Gram-positive bloodstream infections (BSIs) are an emerging health concern, especially in resource-limited settings. There is a paucity of data regarding the antimicrobial resistance (AMR) pattern of Gram-positive BSIs. The rise in multidrug-resistant infections further convoluted antibiotic selection. We aimed to assess the incidence, clinical and microbiological profile, antimicrobial resistance (AMR) and outcome in Gram-positive BSIs. This was a single-center prospective study conducted at a tertiary care hospital in Western India. All patients (age ≥18 years) with culture-proven Gram-positive BSIs were included. Data were collected on all patients' demography, risk factors, AMR and clinical outcome. A total of 210 clinically significant isolates were grown from July 2020 to December 2021. The incidence of Gram-positive BSIs was 29% (n=61); 55.9% of cases were healthcare-associated, while 44.1% were community-acquired. Coagulase-negative staphylococci (CoNS) were the major isolates (36.1%), followed by Enterococcus spp. (27.9%), methicillin-susceptible Staphylococcus aureus (MSSA) (18%) and methicillin-resistant Staphylococcus aureus (MRSA) (14.7%). The proportion of vancomycin and teicoplanin-resistant CoNS isolates was 13.6% and 19%. Among Enterococcus isolates, the proportion of vancomycin-resistant enterococci (VRE) and linezolid-resistant enterococci (LRE) were 11.8% and 5.9%. The overall mortality in Gram-positive BSIs was 42.6%. Older age, MRSA infection, septic shock, and high NLR were significantly associated with mortality. On the Cox regression model, age ≥65 years (HR: 2.5; 95%CI: 1.1-5.8; p=0.024) and MRSA infection (HR: 3.6; 95%CI: 1.5-8.5; p=0.021) were found as independent predictors of 30-day mortality. This study found substantial mortality with Gram-positive BSIs, especially MRSA infections. Moreover, the emergence of VRE and LRE is also alarming. Active surveillance of AMR and evaluation of mortality predictors may help overcome the therapeutic challenges in managing BSIs.

Oral antibiotic step-down therapy for nonstaphylococcal gram-positive bloodstream infections

Bloodstream infections traditionally are treated with intravenous (IV) therapy. This study's purpose is to evaluate if oral step-down therapy is noninferior to IV therapy for gram-positive bloodstream infections (GP-BSIs). This retrospective cohort study included patients who received IV therapy and those who received oral step-down therapy for a nonstaphylococcal GP-BSI from 2017 to 2019. The primary endpoint was a composite outcome of 90-day all-cause mortality and clinical failure. A total of 308 patients were included (n = 94, oral; n = 214, IV). The oral step-down group had a lower incidence of 90-day clinical failure (9% vs 14%; P < 0.001). The IV group had a longer hospital stay (4 vs 6 days, P < 0.001); however, there were no significant differences in secondary outcomes. Bivariate analysis found no predictors of 90-day clinical failure. Oral step-down therapy was found to be noninferior to IV therapy.

Oritavancin vs Standard of Care for Treatment of Nonendovascular Gram-Positive Bloodstream Infections.

Data is limited comparing oritavancin (ORT) to the standard-of-care (SOC) for the treatment gram-positive blood stream infections (BSI). This was a retrospective study of all patients in the Veteran's Affairs Health Care System treated with at least 1 dose of oritavancin or at least 5 days of vancomycin, daptomycin, ceftaroline, ampicillin, ampicillin-sulbactam, nafcillin, oxacillin, or cefazolin for a documented gram-positive BSI from 1 January 2015 to 30 June 2021. Patients with polymicrobial blood cultures or positive cultures from other sites were included if the organisms were sensitive to the incident antimicrobial; no concomitant antimicrobials could be used once the incident agent was started. Individuals were also excluded if they were diagnosed with endocarditis, had a neutrophil count 96-hours of treatment before the incident antimicrobial was started.The primary composite outcome was clinical failure, defined as all-cause mortality within 30-days from the end of therapy, or blood cultures positive for the incident organisms ≥72 hours after administration of the first dose and ≤30 days after the administration of the final dose of the study antimicrobial, or any drug or line-related readmissions within 30-days of hospital discharge. Two hundred-forty patients were identified for screening with 96 meeting criteria (27 in ORT and 69 in SOC groups). Baseline characteristics were generally balanced between groups except more patients in the ORT group received >96-hours of treatment before the incident antimicrobial was started (70.3% (19/27) vs 13.04% 9/69); P < .001). The pathogen most prevalent was methicillin susceptible Staphylococcus aureus (MSSA) (ORT 33.3% (9/27) vs SOC 46.4% (32/69)). Clinical failure occurred in 7.4% (2/27) in the ORT group and 17.4% (12/69) in SOC (P = .34). No components of the primary outcome were significantly different between groups, but AKI did occur more commonly in the SOC group (27.5% (19/69) vs 3.7% (1/27); P = .01). ORT appears to be a safe and effective option when directly compared to the SOC for non-endocarditis BSIs.

Bloodstream infection burden among cancer clinic patients with PICC Lines: A prospective, observational study

Background: Oncology patients are at high risk for bloodstream infection (BSI) due to immunosuppression and frequent use of central venous catheters. Surveillance in this population is largely relegated to inpatient settings and limited data are available describing community burden. We evaluated rates of BSI, clinic or emergency department (ED) visits, and hospitalizations in a large cohort of oncology outpatients with peripherally inserted central catheters (PICCs). Methods: In this prospective, observational study, we followed a convenience sample of adults (age&gt;18) with PICCs at a large academic outpatient oncology clinic for 35 months between July 2015 and November 2018. We assessed demographics, malignancy type, PICC insertion and removal dates, history of prior PICC, and line duration. Outcomes included BSI events (defined as &gt;1 positive blood cultures or &gt;2 positive blood cultures if coagulase-negative Staphylococcus), ED visits (without hospitalization), and unplanned hospitalizations (excluding scheduled chemotherapy hospitalizations). We used χ2 analyses to compare the frequency of categorical outcomes, and we used unpaired t tests to assess differences in means of continuous variable in hematologic versus solid-tumor malignancy patients. We used generalized linear mixed-effects models to assess differences in BSI (clustered by patient) separately for gram-positive and gram-negative BSI outcomes. Results: Among 478 patients with 658 unique PICC lines and 64,190 line days, 271 patients (413 lines) had hematologic malignancy and 207 patients (232 lines) had solid-tumor malignancy. Cohort characteristics and outcomes stratified by malignancy type are shown in Table 1. Compared to those with hematologic malignancy, solid-tumor patients were older, had 47% fewer clinic visits, and had 32% lower frequency of prior PICC lines. Overall, there were 75 BSI events (12%; 1.2 per 1,000 catheter days). We detected no significant difference in BSI rates when comparing solid-tumor versus hematologic malignancies (P = 0.20); BSIs with gram-positive pathogen were 69% higher in patients with solid tumors. Gram-negative BSIs were 41% higher in patients with hematologic malignancy. Solid-tumor malignancy was associated with 4.5-fold higher odds of developing BSI with gram-positive pathogen (OR, 4.48; 95% CI, 1.60–12.60; P = .005) compared to those with hematologic malignancy, after adjusting for age, sex, history of prior PICC, and line duration. Differences in gram-negative BSI were not significant on multivariate analysis. Conclusions: The burden of all-cause BSIs in cancer clinic adults with PICC lines was 12% or 1.2 per 1,000 catheter days, as high as nationally reported inpatient BSI rates. Higher risk of gram-positive BSIs in solid-tumor patients suggests the need for targeted infection prevention activities in this population, such as improvements in central-line monitoring, outpatient care, and maintenance of lines and/or dressings, as well as chlorhexidine bathing to reduce skin bioburden.Disclosures: None

Risk of bloodstream infections in allogeneic hematopoietic cell transplant recipients according to gut mucosal colonization and fluoroquinolone implementation during neutropenia

Background . Higher rate of gram-negative bloodstream infections (BSI) have been recently documented from transplantation centers providing fluoroquinolone (FQ) prophylaxis. Aim . To define the incidence of BSI during neutropenia according to gut mucosal colonization with resistant gramnegative bacteria and FQ administration. Materials and methods . Of 284 allogeneic hematopoietic cell transplant recipients included in the study, 154 (54.2 %) were identified as colonized with resistant gram-negative bacteria, and 130 (45.8 %) patients as non-colonized. Resistant gram-negative bacteria included Enterobacterales with extended spectrum beta-lactamase production, carbapenem-resistant Enterobacterales, Stenotrophomonas maltophilia , and carbapenem-resistant strains of Pseudomonas aeruginosa . Colonized patients did not receive FQ prophylaxis (n = 147) except 7 patients who received FQ as sequential therapy due to residual inflammatory lung lesions. Among non-colonized patients 98 received FQ prophylaxis, whereas 32 did not. Results . Probability of gram-negative BSI (71.4 %; p &lt;0.0001), and extended spectrum beta-lactamase-producing Enterobacterales BSI (57.1 %; p &lt;0.0001) was significantly higher in colonized patients receiving FQ. No significant difference was found in probability of gram-positive BSI (p = 0.452). In multivariate analysis colonized patients with (hazard ratio (HR) 35.32; 95 % confidence interval (CI) 9.15–136.44; p &lt;0.0001) or without FQ (HR 3.44; 95 % CI 1.15–10.31; p = 0.007), omission of FQ in non-colonized patients (HR 4.03; 95 % CI 1.08–15.00; p = 0.038), and active disease before allogeneic hematopoietic cell transplantation (HR 2.17; 95 % CI 1.03–4.63; p = 0.042) were associated with higher risk of gram-negative BSI, whereas mismatched unrelated donor transplantations were associated with higher gram-positive BSI risk (HR 3.84; 95 % CI 1.63–9.08; p = 0,009). Conclusion . Colonization with multiresistant gram-negative bacteria is a predictor of gram-negative BSI, including multiresistant pathogens, especially when FQ are prescribed during neutropenia, while in non-colonized patients FQ prophylaxis is an effective approach significantly reducing gram-negative BSI.

Oral stepdown in Gram-positive bloodstream infections: A step in the right direction.

Bloodstream infections (BSIs) due to Gram-positive organisms have traditionally been treated with prolonged courses of intravenous antimicrobials. However, this dogma is associated with substantial burden to the patient and health care system. Consequently, there is growing interest in the utilization of oral stepdown therapy, defined as the transition of intravenous therapy to an active oral agent, for this indication. This review highlights available literature examining oral stepdown in adult patients with BSI due to commonly encountered Gram-positive pathogens, including Staphylococcus aureus, Streptococcus spp., and Enterococcus spp. Support for oral stepdown in this setting is primarily derived from observational studies subject to selection bias. Nevertheless, this treatment strategy exhibits promising potential in carefully selected patients as it is consistently associated with reductions in hospital length of stay without jeopardizing clinical cure or survivability. Prospective, randomized trials are needed for validation of oral stepdown in Gram-positive BSI and to identify the optimal patient population and regimen.

Clearance of blood stream infections in patients receiving extracorporeal membrane oxygenation: a retrospective single-center cohort study

BackgroundThere are limited data on the treatment of blood stream infections (BSIs) in patients receiving extracorporeal membrane oxygenation (ECMO). Current guidance recommends documenting clearance only in fungal and Gram-positive BSIs. This study investigates the incidence and clinical significance of blood stream infections with positive repeat cultures (BSIPRC) in ECMO as well as clinical factors that may predict positive repeat cultures.MethodsAll BSIs in patients receiving ECMO at Brooke Army Medical Center between September 2012 and October 2021 were included in this study. BSIPRC was defined as re-isolation of the same organism on repeat blood cultures following an initial positive blood culture.ResultsA total of 60 patients developed 87 BSI (38.5 BSI per 1000 ECMO days). Of the 80 (92%) BSIs who had repeat blood cultures drawn, patients had BSIPRC in 35 (44%) of cases. Fever, leukocytosis, and vasopressor requirement on day of repeat culture were not associated with persistent positivity. There was no difference in survival to discharge for patients with BSIPRC as compared to single day BSI (58% vs. 63%, p = 0.78). 19% of patients with Gram-negative bacteremia had BSIPRC, and gram-negative bacteremia in general was associated with an 83% morality.ConclusionsThere were no clinical findings that differentiated patients with BSIPRC from those who had a single day of positivity. BSI was associated with high mortality in patients with Gram-negative bacteremia. Given high incidence of positive repeat cultures being seen in Gram-negative BSIs, repeat blood cultures have utility for all BSIs in patients receiving ECMO.

1845. Oritavancin Compared to the Standard-of-Care for the Treatment of Gram-positive Blood Stream Infections

Abstract Background Data is limited comparing oritavancin (ORT) to the standard-of-care (SOC) for the treatment gram-positive blood stream infections (BSI). Methods This was a retrospective study of all patients in the Veteran’s Affairs Health Care System treated with at least 1 dose of oritavancin or at least 5 days of vancomycin, daptomycin, ceftaroline, ampicillin, ampicillin-sulbactam, nafcillin, oxacillin, or cefazolin for a documented gram-positive BSI from 1 January 2015 to 30 June 2021. Patients with polymicrobial blood cultures or positive cultures from other sites were included if the organisms were sensitive to the incident antimicrobial; no concomitant antimicrobials could be used once the incident agent was started. Individuals were also excluded if they were diagnosed with endocarditis, had a neutrophil count &amp;lt; 500 cells/mm3, or had a diagnosis of Human Immunodeficiency Virus (HIV) on their problem list. The primary composite outcome was clinical failure, defined as all-cause mortality within 30-days from the end of therapy, or blood cultures positive for the incident organisms ≥72 hours after administration of the first dose and ≤30 days after the administration of the final dose of the study antimicrobial, or any drug or line-related readmissions within 30-days of hospital discharge. Secondary outcomes included all-cause 30-day readmission and rates of acute kidney injury (AKI). Results Two hundred-forty patients were identified for screening with 96 meeting criteria (27 in ORT and 69 in SOC groups). Baseline characteristics were generally balanced between groups except more patients in the ORT group received &amp;gt; 96-hours of treatment before the incident antimicrobial was started (70.3% (19/27) vs. 13.04% (9/69); p&amp;lt;0.001). The pathogen most prevalent was methicillin-susceptible Staphylococcus aureus (MSSA) (ORT 33.3% (9/27) vs. SOC 46.4% (32/69)). Clinical failure occurred in 7.4% (2/27) in the ORT group and 17.4% (12/69) in SOC (p=0.34). No components of the primary outcome were significantly different between groups, but AKI did occur more commonly in the SOC group (27.5% (19/69) vs. 3.7% (1/27); p=0.01). Conclusion ORT appears to be a safe and effective option when directly compared to the SOC for non-endocarditis BSIs. Disclosures Ryan P. Moenster, Pharm.D., FIDSA, Melinta Therapeutics: Grant/Research Support|Melinta Therapeutics: Honoraria.

1815. Assessment of Therapy Duration for Non-Staphylococcal Gram-Positive Bloodstream Infections

Abstract Background The optimal duration of antimicrobial therapy for non-staphylococcal Gram-positive (GP) bloodstream infections (BSIs) remains unknown. The purpose of this study was to evaluate clinical outcomes in patients with short (6-10 days) vs. long (11-21 days) duration of therapy (DOT) for non-staphylococcal GP BSIs. Methods Adult patients with BSI due to Streptococcus or Enterococcus spp. admitted to a community health system from January 2016 to December 2021 were included in this retrospective chart review. Patients were excluded for polymicrobial BSI, positive culture deemed contamination, infectious source requiring prolonged treatment, DOT &amp;lt; 6 or &amp;gt; 21 days, or transfer, hospice, or death prior to therapy completion. The primary endpoint was 90-day all-cause mortality. Descriptive statistics, chi-square or Fisher’s exact test, and the student t-test were used for data analysis. Results Of 3,544 patients identified, 384 were screened and 86 included. There were 71 patients in the long DOT group and 15 patients in the short DOT group. All included patients were on active therapy for the entire DOT. Baseline characteristics were similar except patients in the long DOT group were more likely to have an infectious diseases consultation and a non-pulmonary source of infection (Table 1). All-cause mortality at 90 days was similar between short vs. long DOT groups (0% vs. 3%, p=0.51) (Table 2). The secondary endpoints of 30-day all-cause mortality, 30-day and 90-day BSI recurrence due to the same organism, 30-day readmission, and hospital length of stay were not statistically different between groups (Table 2). The most common pathogen identified in the short DOT group was Streptococcus pneumoniae (n=8), and the most common identified pathogens identified in the long DOT group was Streptococcus agalactiae (n=22), Enterococcus faecalis (n=14), and S. pneumoniae (n=13) (Table 3). Conclusion In this retrospective review of non-staphylococcal GP BSIs, there was no statistical difference in clinical outcomes between the short and long DOT arms. Additional research is needed to identify the optimal duration of antimicrobial therapy for non-staphylococcal GP BSIs. Disclosures All Authors: No reported disclosures.

2015. Challenges in Assessing Blood Stream Infection Clearance in Patients Receiving Extracorporeal Membrane Oxygenation

Abstract Background There is a limited published data on the treatment of blood stream infections (BSI) in patients receiving extracorporeal membrane oxygenation (ECMO). Traditionally, the management of only fungal and Gram-positive BSIs require follow-up blood cultures to document clearance. The presence of large retained cannulas in ECMO create concern for persistent bacteremia. This study investigates whether certain variables are predictive of blood stream infections with positive repeat cultures (BSIPRC) and if BSIPRC is associated with increased mortality. Methods All positive blood cultures from patients receiving ECMO at Brooke Army Medical Center identified between September 2012 and October 2021 were included in this study. Blood cultures were excluded if they were determined to be contaminants by the primary team. For each positive blood culture, charts were retrospectively reviewed. Date of clearance was defined as the first negative blood culture after a positive. BSIPRC was defined as re-isolation of the same organism on repeat blood cultures following an initial positive blood culture. Results A total of 60 patients and 87 BSI were investigated (38.5 BSI per 1000 ECMO days). Gram-positive (GP) organisms caused a majority of BSI (n=52, 60%) followed by Gram-negative (GN) (n=22, 25%) and fungal (n=13, 15%) infections. Of the 80 (92%) BSIs who had repeat blood cultures drawn, patients had BSIPRC in 35 (44%) of cases. There were no clinical features that differentiated patients with positive repeat cultures (Table). There was no difference in survival to discharge for patients with BSIPRC as compared to single day BSI (20 (58%) vs. 28 (63%), p=0.78). In 6 patients with BSIPRC with Gram-negative organisms, two (33%) died before clearance and five (83%) died before decannulation. Characteristics of patients and all blood stream infections. Conclusion There were no clinical findings that differentiated patients with BSIPRC from those who had a single day of positivity. BSIPRC was associated with high mortality in patients with Gram-negative bacteremia. In the absence of clear predicative factors in demonstrating clearance of BSI, repeat blood cultures may be necessary. Future studies are needed to determine why Gram-negative BSIPRC are associated with a high mortality. Disclosures All Authors: No reported disclosures.

P39 Bloodstream infections (BSI) in tertiary ICU—an update!

BackgroundPatients in ICU represent a small proportion of inpatients; however they account for up to 25% of all hospital acquired infections (HAI) and are 2–5 times more likely to develop a HAI than the average patient. Management of bloodstream infections (BSI) in ICU is a rising problem due to increasing antibiotic resistance posing challenges to antimicrobial stewardship (AMS) leading to higher mortality in ITU patients. It increases duration of inpatient stay, hospital costs and worsens prognosis.ObjectivesTo find all-cause mortality in patients with BSI admitted to intensive care at 14 and 28 days from admission.MethodsWe used retrospective patient data from the hospital database between March 2019 to March 2020.ResultsWe included 113 patients admitted to ICU and had BSI, of which 12.4% died at 14 days and 24.8% died at 28 days with overall mortality of 33.6% at discharge. Respiratory comorbidity was found significantly higher (48.1%). Patients with Gram-negative BSI had higher mortality with 14.29% at 14 days when compared with Gram-positive BSI, but 28 day mortality was similar in both groups (25.71% and 25% respectively), which is concerning.ConclusionsThis study concludes that patients admitted to ICU have higher mortality at 28 days irrespective of the pathogen isolated in the bloodstream. This could be explained due to prolonged stay in ICU leading to increased burden from HAI. Future AMS will have to focus on a prevention model for this cohort to improve patient outcome.

Characteristics and Outcomes of Bloodstream Infections in a Tertiary-Care Pediatric Hematology-Oncology Unit: A 10-Year Study.

Bloodstream infections (BSIs) after chemotherapy or hematopoietic stem cell transplantation (HSCT) are a leading cause of morbidity and mortality. Data on 154 BSIs that occurred in 111 onco-hematological patients (57 hematological malignancies, 28 solid tumors, and 26 non-malignant hematological diseases) were retrospectively collected and analyzed. Monomicrobial Gram-positive (GP), Gram-negative (GN), and fungal BSIs accounted for 50% (77/154), 38.3% (59/144), and 3.2% (5/154) of all episodes. Polymicrobial infections were 7.8% (12/154), while mixed bacterial–fungal infections were 0.6% (1/154). The most frequent GN isolates were Escherichia coli (46.9%), followed by Pseudomonas aeruginosa (21.9%), Klebsiella species (18.8%), and Enterobacter species (6.3%). Overall, 18.8% (12/64) of GN organisms were multidrug-resistant (seven Escherichia coli, three Klebsiella pneumoniae, and two Enterobacter cloacae), whereas GP resistance to glycopeptides was observed in 1% (1/97). Initial empirical antibiotic therapy was deemed inappropriate in 12.3% of BSIs (19/154). The 30-day mortality was 7.1% (11/154), while the bacteremia-attributable mortality was 3.9% (6/154). In multivariate analysis, septic shock was significantly associated with 30-day mortality (p = 0.0001). Attentive analysis of epidemiology and continuous microbiological surveillance are essential for the appropriate treatment of bacterial infections in pediatric onco-hematological patients.